Clinical Significance of Elevated Neuron-Specific Enolase (NSE) Levels
Elevated Neuron-Specific Enolase (NSE) levels in patients primarily indicate neuronal damage and serve as a biomarker for various neurological conditions, with highest clinical utility in post-cardiac arrest prognostication when used in combination with other neurological assessments.
What is NSE?
- NSE is a glycolytic enzyme enriched in neuronal cell bodies, making it a suitable marker of neuronal damage 1
- It exists as γγ- and αγ-dimers and is highly specific for neurons and peripheral neuroendocrine cells 2
- NSE is released following injury to neurons, with blood values likely correlating with the extent of anoxic-ischemic neurological injury 1
Clinical Applications of NSE
Post-Cardiac Arrest Prognostication
- NSE levels in CSF are proportional to traumatic brain injury (TBI) severity and associated with increased mortality rates in moderate or severe TBI 1
- In post-cardiac arrest patients, NSE levels >33 μg/L at any time from day 1 to 3 appear to predict poor neurological outcome 1
- NSE levels are decreased in subjects treated with hypothermia over time (to 48 hours), suggesting its potential utility in monitoring treatment efficacy 1
- The discriminative value of NSE levels at 48-72 hours is higher than at 24 hours, with increasing NSE levels over time having additional value in predicting poor outcome 1
Neurological Disorders
- Elevated NSE is found in patients with seizures, with a close correlation between NSE levels and seizure frequency 3
- NSE serves as a quantitative measure of brain damage in ischemic stroke, intracerebral hemorrhage, seizures, and traumatic brain injury 2
- Significantly higher NSE levels are observed in critically ill neurology patients with seizures compared to those without seizures 3
Oncology
- NSE is the most reliable tumor marker for diagnosis, prognosis, and follow-up of small cell lung cancer (SCLC) 2
- NSE levels correlate with tumor burden, number of metastatic sites, and response to treatment in neuroendocrine tumors 2
- Raised serum levels of NSE are found in all stages of neuroblastoma, with greater concentration increases in widespread and metastatic disease 2
Limitations and Caveats
- NSE should not be used alone to predict neurological outcomes due to the possibility of high false-positive rates 1
- Laboratory standards for NSE measurement vary between centers, making comparison of absolute values difficult 1
- NSE is sensitive to hemolysis, which is a significant limitation for its use as a serum biomarker 1
- NSE is not specific to neuronal damage and can be produced by extra-central nervous system sources including:
Best Practice Recommendations
- When evaluating post-cardiac arrest patients, consider high serum values of NSE at 48 to 72 hours after cardiac arrest to support the prognosis of poor neurological outcome, but only when performed with other prognostic tests 1
- Serial measurements showing persistently high or increasing NSE values provide more reliable prognostic information than single measurements 1
- For post-cardiac arrest prognostication, use NSE as a confirmatory test rather than a primary method for estimating prognosis 1
- Take care when drawing blood samples for NSE measurement to avoid hemolysis, which can lead to false-positive results 1
Emerging Research
- Recent studies suggest NSE may play dual roles in both neuroinflammation and neuroprotection depending on the injury, disease, and microenvironment 4
- NSE may control neuronal survival, differentiation, and neurite regeneration via activation of PI3K and MAPK signaling pathways 4
- Methodological approaches for NSE evaluation need improvement, as current ELISA methods may not differentiate between heterodimers of enolases or assess enzymatic activity 5
In conclusion, while NSE is a valuable biomarker of neuronal injury across multiple conditions, its greatest clinical utility is in post-cardiac arrest prognostication when used as part of a multimodal assessment approach rather than in isolation.